Transmissible spongiform encephalopathies (TSEs) can be associated with blood infectivity. Many patients dying with Creutzfeldt-Jakob disease (CJD) have donated blood in the years before they become ill, and a major concern has arisen about the risk of transmitting disease through the administration of contaminated blood or blood products. Infectivity in blood components and Cohn plasma fractions was examined in two different experimental studies: (1) high input infectivity in normal human blood that had been "spiked" with a suspension of trypsinized intact cells from a scrapie-infected hamster brain, and (2) low (indigenous) infectivity in the blood of mice inoculated with a mouse- adapted strain of human CJD. Infectivity was assayed by intracerebral inoculation of normal hamsters (scrapie or mice CJD). High levels of scrapie "spike" infectivity were recovered in all blood components, cryoprecipitate, and fraction I + II + III, with considerably less infectivity in the last two fractions. CJD-infected mice had very low ow levels of infectivity in buffy coat, plasma, plasma cryoprecipitate, and plasma fraction I + II + III, and no infectivity in the last two fractions. Thus, the potential risk of CJD transmission from buffy coat, plasma, factor VIII, or immune globulin (derived from the first two Cohn fractions) appears to be very low, and to be nonexistent for factor IX complex and albumin (derived from the last two fractions).